1. Molecular mechanisms underlying the manifestation of symptoms in schizophrenia.
2. Neurobiology of autism.
Molecular mechanisms underlying the manifestation of symptoms in schizophrenia:
This line of research involves studying acute and chronic changes in the levels of phosphoproteins, signalling intermediates, transcription factors and target gene expression in key areas in the brain following administration of antipsychotic drugs and psychotropic drugs in animals, and studying molecular changes in animal models of schizophrenia. A number of molecular biological, neuroanatomical and behavioural methods in combination with intracerebral administration of drugs/blockers/siRNA are employed in awake, behaving animals. Expected results may further our understanding of molecular mechanisms underlying schizophrenic symptoms and may point to potential novel therapeutic targets.
Collaborator: Dr. W.J. Rushlow, Department of Psychiatry
• Alimohamad, H., Sutton, L., Mouyal, J., Rajakumar, N. and Rushlow, W.J. (2005) The effects of antipsychotics on beta-catenin, glycogen synthase kinase-3 and dishevelled in the ventral midbrain of rats. J Neurochem . 95(2): 513-25.
• Rushlow, W.J., Seah, Y.H., Belliveau, D.J. and Rajakumar, N. (2005) Changes in calcineurin expression induced in the rat brain by the administration of antipsychotics. J Neurochem. Aug; 94(3): 587-96.
• Alimohamad, H., Rajakumar, N., Seah, Y.H. and Rushlow, W. (2005) Antipsychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum. Biol Psychiatry . Mar 1; 57(5): 533-42.
• Rajakumar, N., Leung, L.S., Ma, J., Rajakumar, B. and Rushlow, W. (2004) Altered neurotrophin receptor function in the developing prefrontal cortex leads to adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition of acoustic startle. Biol Psychiatry. Apr 15; 55(8): 797-803.
Neurobiology of autism:
This line of research involves in vivo magnetic resonance (MR) spectroscopic and volumetric imaging in patients, and parallel studies to develop a suitable rat model of autism. Images obtained with MR will be used in sophisticated computer modeling to analyse differences between patients and age-matched controls. Animal studies employ molecular perturbations of developing brain in combination with molecular biological, histological and behavioural analysis of changes.
Collaborator: Dr. R. Nicholson, Department of Psychiatry
• Nicolson, R., Devito, T.J., Vidal, C.N., Sui, Y., Hayashi, K.M., Drost, D.J., Williamson, P.C., Rajakumar, N., Toga, A.W. and Thompson, P.M. (2006) Detection and mapping of hippocampal abnormalities in autism. Psychiatry Res. 2006 Oct 20; [Epub ahead of print].
• Vidal, C.N., Nicolson, R., DeVito, T.J., Hayashi, K.M., Geaga, J.A., Drost, D.J., Williamson, P.C., Rajakumar, N., Sui, Y., Dutton, R.A., Toga. A.W. and Thompson, P.M. (2006) Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity. Biol Psychiatry. Aug 1; 60(3): 218-25.
• Hendry, J., DeVito, T., Gelman, N., Densmore, M., Rajakumar, N., Pavlosky, W., Williamson, P.C., Thompson, P.M., Drost, D.J. and Nicolson, R. (2006) White matter abnormalities in autism detected through transverse relaxation time imaging. Neuroimage. 2006 Feb 15; 29(4): 1049-57.